CD4+ T-Cell Responses Mediate Progressive Neurodegeneration in Experimental Ischemic Retinopathy

Vu, T. H. Khanh; Chen, Huihui; Pan, Li; Cho, Kin‐Sang; Doesburg, Djoeke; Thee, Eric F.; Wu, Nan; Arlotti, Elisa; Jager, Martine J.; Chen, Dong Feng

doi:10.1016/j.ajpath.2020.04.011

Cited by 24 publications

(26 citation statements)

References 42 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Analysis with flow cytometry using CD11b and CD45 double-immunolabeling revealed an early increase in numbers of microglia (CD11b high CD45 mid ) and macrophages (CD11b high CD45 high ) that were peaked on day 7 post RI in mice ( Figures 3B-D), similar to that were seen in rats. We previously showed that RI also induced retinal infiltration of lymphocytes, particularly CD4 + IFN-g-producing T helper (Th1) cells, which participate in the propagation of RGC damage (24). We confirmed that CD4 + T cell infiltration into the retina was peaked on day 14 after RI (P = 0.021) ( Figure 3E), a week later after microglial and macrophage activations reached their peaks.…”

Section: Therapeutic Administration Of Anti-csf1r Attenuated Ri-inducsupporting

confidence: 77%

“…Importantly, weekly administration of CSF-1RAb in our study is sufficient to maintain the suppression of microglial, macrophage, and T cell activations beyond 14 days post injury. Our previous studies suggested a critical role for retinal immune responses in the etiology of neurodegeneration associated with both acute RI-induced and chronic glaucomatous optic nerve damage (24,25); the prolonged phase of the immune responses offers a therapeutic window for preserving vision after RI. The present research demonstrated an early onset of microglia/macrophage activation that proceeds lymphocyte and T cell infiltration and provides an attractive target for therapeutic interventions.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Therapeutic Targeting of Retinal Immune Microenvironment With CSF-1 Receptor Antibody Promotes Visual Function Recovery After Ischemic Optic Neuropathy

et al. 2020

Self Cite

View full text Add to dashboard Cite

Section: Therapeutic Administration Of Anti-csf1r Attenuated Ri-inducsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Therapeutic Targeting of Retinal Immune Microenvironment With CSF-1 Receptor Antibody Promotes Visual Function Recovery After Ischemic Optic Neuropathy

et al. 2020

Self Cite

View full text Add to dashboard Cite

“…In response to perturbations in the retina and the brain, innate immunity can be rapidly activated through transcriptional and phenotypic alterations of immune glial cells and the release of inflammatory cytokines [ 25 , 26 ]. However, excessive activation of innate immune reactivity under injury or traumatic stress can promote further activation of adaptive immunity by antigen-presenting cells that attract and guide peripheral immune cells, such as T cells to the injury sites [ 27 – 29 ]. Neuroinflammation has been well documented as a pathological factor in neuronal death in the brain and in retinal disorders.…”

Section: Introductionmentioning

confidence: 99%

Baicalein, Baicalin, and Wogonin: Protective Effects against Ischemia‐Induced Neurodegeneration in the Brain and Retina

Pan

Cho

et al. 2021

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

Ischemia is a common pathological condition present in many neurodegenerative diseases, including ischemic stroke, retinal vascular occlusion, diabetic retinopathy, and glaucoma, threatening the sight and lives of millions of people globally. Ischemia can trigger excessive oxidative stress, inflammation, and vascular dysfunction, leading to the disruption of tissue homeostasis and, ultimately, cell death. Current therapies are very limited and have a narrow time window for effective treatment. Thus, there is an urgent need to develop more effective therapeutic options for ischemia-induced neural injuries. With emerging reports on the pharmacological properties of natural flavonoids, these compounds present potent antioxidative, anti-inflammatory, and antiapoptotic agents for the treatment of ischemic insults. Three major active flavonoids, baicalein, baicalin, and wogonin, have been extracted from Scutellaria baicalensis Georgi (S. baicalensis); all of which are reported to have low cytotoxicity. They have been demonstrated to exert promising pharmacological capabilities in preventing cell and tissue damage. This review focuses on the therapeutic potentials of these flavonoids against ischemia-induced neurotoxicity and damage in the brain and retina. The bioactivity and bioavailability of baicalein, baicalin, and wogonin are also discussed. It is with hope that the therapeutic potential of these flavonoids can be utilized and developed as natural treatments for ischemia-induced injuries of the central nervous system (CNS).

show abstract

“…The Tregs can migrate to the diseased tissue and dampen inflammation by increasing the milieu of anti-inflammatory cytokines and activating macrophages to clear the debris and restore the damaged tissue [ 15 , 16 , 17 ]. Since CD4+ T cells may mediate retinal ganglion cell (RGC) degeneration and loss of retinal function after injury [ 18 ], it may be possible to reprogram the CD4+ T cells at the site of injury to acquire a Treg phenotype. This might aid in the rescue of retinal damage and, as a result, decrease cell loss and enhance immunotolerance [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell Induced Foxp3(+) Tregs Suppress Effector T Cells and Protect against Retinal Ischemic Injury

Agrawal

Rasiah

Bajwa

et al. 2021

Cells

View full text Add to dashboard Cite

Mesenchymal stem/stromal cells (MSC) are well known for immunomodulation; however, the mechanisms involved in their benefits in the ischemic retina are unknown. This study tested the hypothesis that MSC induces upregulation of transcription factor forkhead box protein P3 (Foxp3) in T cells to elicit immune modulation, and thus, protect against retinal damage. Induced MSCs (iMSCs) were generated by differentiating the induced pluripotent stem cells (iPSC) derived from urinary epithelial cells through a noninsertional reprogramming approach. In in-vitro cultures, iMSC transferred mitochondria to immune cells via F-actin nanotubes significantly increased oxygen consumption rate (OCR) for basal respiration and ATP production, suppressed effector T cells, and promoted differentiation of CD4+CD25+ T regulatory cells (Tregs) in coculture with mouse splenocytes. In in-vivo studies, iMSCs transplanted in ischemia-reperfusion (I/R) injured eye significantly increased Foxp3+ Tregs in the retina compared to that of saline-injected I/R eyes. Furthermore, iMSC injected I/R eyes significantly decreased retinal inflammation as evidenced by reduced gene expression of IL1β, VCAM1, LAMA5, and CCL2 and improved b-wave amplitudes compared to that of saline-injected I/R eyes. Our study demonstrates that iMSCs can transfer mitochondria to immune cells to suppress the effector T cell population. Additionally, our current data indicate that iMSC can enhance differentiation of T cells into Foxp3 Tregs in vitro and therapeutically improve the retina’s immune function by upregulation of Tregs to decrease inflammation and reduce I/R injury-induced retinal degeneration in vivo.

show abstract

CD4+ T-Cell Responses Mediate Progressive Neurodegeneration in Experimental Ischemic Retinopathy

Cited by 24 publications

References 42 publications

Therapeutic Targeting of Retinal Immune Microenvironment With CSF-1 Receptor Antibody Promotes Visual Function Recovery After Ischemic Optic Neuropathy

Therapeutic Targeting of Retinal Immune Microenvironment With CSF-1 Receptor Antibody Promotes Visual Function Recovery After Ischemic Optic Neuropathy

Baicalein, Baicalin, and Wogonin: Protective Effects against Ischemia‐Induced Neurodegeneration in the Brain and Retina

Mesenchymal Stem Cell Induced Foxp3(+) Tregs Suppress Effector T Cells and Protect against Retinal Ischemic Injury

Contact Info

Product

Resources

About